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Biomedical subjects

S L Romney

Publications and source records attributed to S L Romney.

At least 19 recordsLinked to original sources

Beta-carotene levels in exfoliated cervicovaginal epithelial cells in cervical intraepithelial neoplasia and cervical cancer.

OBJECTIVE: The purpose of this study was to measure beta-carotene levels in exfoliated epithelial cervicovaginal cells collected by a lavage technique in normal women and patients with histopathologically diagnosed cervical intraepithelial neoplasia and cervical cancer. STUDY DESIGN: In a cross-sectional sampling of women (n = 105), cervicovaginal cells and plasma beta-carotene levels were assayed with high-pressure liquid chromatography. In addition, beta-carotene levels were measured in exfoliated epithelial samples of cervicovaginal cells obtained from women (n = 24) enrolled in an ongoing oral beta-carotene supplementation clinical trial. RESULTS: Cervicovaginal cells and plasma beta-carotene levels were found to be significantly decreased in women with cervical intraepithelial neoplasia and cervical cancer as compared with controls (p < 0.0001, analysis of variance). Retinol levels in cervicovaginal cells were undetectable. The beta-carotene levels in cervicovaginal cells were markedly increased in the majority of patients (79%) after oral supplementation as compared with baseline levels in women enrolled in the beta-carotene clinical trial. CONCLUSION: The study demonstrates that changes of in situ cellular beta-carotene concentrations are measurable in samples of exfoliated epithelial cells obtained by a noninvasive saline lavage harvesting technique. The current findings further support our previous hypothesis that beta-carotene deficiency may have an etiologic role in the pathogenesis of cervical intraepithelial neoplasia and/or cervical cancer.

Adolescent

Factors influencing the exfoliation of cervicovaginal epithelial cells.

OBJECTIVE: Our objective was to investigate the association of smoking and exfoliation of cervicovaginal epithelial cells while controlling for other factors that may potentially influence cell exfoliation (e.g., presence of cervical intraepithelial neoplasia or koilocytes, the use of oral contraceptives, age, and the phase of the menstrual cycle). STUDY DESIGN: Cervicovaginal lavage specimens and epidemiologic questionnaires were obtained with informed consent from 190 women. The cervicovaginal lavage samples were processed to separate other contaminants. The number of squamous epithelial cells counted was expressed as cells per milliliter of lavage. RESULTS: Multiple linear regression analysis revealed that the number of exfoliated epithelial cells was significantly higher in smokers (p < 0.01) and also in women with cervical intraepithelial neoplasia (p < 0.05). The other studied variables had no detectable effect. CONCLUSION: The findings suggest that smoking or the presence of cervical intraepithelial neoplasia may induce an acceleration in the exfoliation of cervicovaginal epithelial cells. This may alter cell maturation and may be a factor in the oncogenic process.

Adolescent

Biologic characteristics of specific human papillomavirus types predicted from morphology of cervical lesions.

Human papillomavirus (HPV) DNA was detected by Southern blot hybridization in cervicovaginal lavage samples from 199 of 329 (60.5%) women attending a municipal hospital colposcopy clinic. Human papillomavirus was identified in 195 of 264 (73.9%) patients with a squamous intraepithelial lesion or cancer on biopsy or Papanicolaou smear (Bethesda system) compared with 11 of 65 (16.9%) without squamous intraepithelial lesion (P < .0001). The most common HPV type identified was HPV 16 (20.6% of positive samples), and 36.7% of isolates contained uncharacterized HPVs. Of women with cervical intraepithelial neoplasia (CIN) grade III or cancer, 23.4% were infected with HPV 16 compared with less than 4% with any other single HPV type. Based on biopsy diagnosis in patients infected with specific HPV types, HPVs 6 and 11 had low oncogenic potential; HPVs 18, 31, 35, and 45 had intermediate oncogenic potential; and HPVs 16 and 33 had high oncogenic potential. Hyperchromatic, unusually enlarged nuclei ("meganuclei"), and/or abnormal mitoses were found significantly more often in lesions infected with HPVs 16, 33, and 35 than in those infected with HPVs 6, 11, 18, 31, and 45, even in low-grade lesions, and may represent a histologic marker for HPVs with significant oncogenic potential. Human papillomavirus capsid protein was detected significantly less often by immunocytochemical staining in CIN I and CIN II lesions infected with HPVs 16 and 33 (8.3%) than in those infected with HPVs 6, 11, 18, and 31 (60%; P = .007), suggesting early abnormalities in cellular differentiation in lesions infected with highly oncogenic HPVs.

Antigens, Viral

Endogenous estradiol and progesterone concentrations in smokers on oral contraceptives.

The simultaneous effects of cigarette smoking and oral contraceptives on serum estradiol and progesterone levels were investigated in 114 premenopausal women. Serum 17 beta-estradiol and progesterone levels were measured by radioimmunoassay. In smokers, estradiol and progesterone levels were significantly lower (p less than 0.025). In smokers using oral contraceptives, estradiol and progesterone levels were the lowest (p less than 0.001 and p less than 0.01, respectively). The findings suggest that smoking and oral contraceptives independently lower serum estradiol and progesterone concentrations in premenopausal women and that the effects may be additive.

Adolescent

Clinical usefulness of computerized colposcopy: image analysis and conservative management of mild dysplasia.

OBJECTIVES: The purposes of this study were to evaluate the clinical usefulness of computerized colposcopy and image analysis, to investigate the correlation between lesion size and grade of dysplasia, and to examine and record the colposcopic changes associated with progression or regression of cervical dysplasia. METHODS: Sixty-eight patients with a fully visualized squamocolumnar junction and a histopathologic diagnosis of mild dysplasia were serially monitored for a period of 1 year using computerized colposcopy and image analysis. All patients had baseline computer-assisted measurements of their cervical lesions and repeat measurements at 3-month intervals. RESULTS: The mean age of the patients was 31 years, and the mean size of the colposcopically visualized lesions was 58 mm2. During the 12-month observation, 5.9% of the lesions increased in size, 32.4% decreased in size, 13.2% remained unchanged, 20.6% disappeared, and 27.9% completely changed location. In patients with an increase in lesion size (N = 4), a repeat biopsy was performed, revealing a progression to moderate dysplasia. Treatment was withheld from patients whose lesions disappeared (N = 14), decreased in size (N = 22), or remained unchanged (N = 9). Active therapy was unnecessary in 66% of cases and repeat biopsy was avoided in 94.1%. CONCLUSIONS: Computerized colposcopy provides objective information and may be an adjunct to cytology and histopathology in some cases. Computerized colposcopy replaces subjective colposcopic evaluation with objective computer assessment and may hold promise for conservative management of cervical dysplasia.

Adult

Plasma levels of antioxidant beta-carotene and alpha-tocopherol in uterine cervix dysplasias and cancer.

Chronic human health problems, namely arteriosclerosis, myocardial ischemia, and cancer, may be caused by highly active oxygen species and may be preventable by antioxidant vitamins. In humans, the sources of two major antioxidants, beta-carotene and alpha-tocopherol, are dietary. In this study, we measured the plasma concentrations of beta-carotene and alpha-tocopherol by reverse-phase high-pressure liquid chromatography in a cross-sectional sampling of 116 women. Significantly reduced plasma levels of beta-carotene and alpha-tocopherol were observed in women with histopathologically diagnosed cervical dysplasias or cancer (p less than 0.0001 and p less than 0.005, respectively). There was an inverse association between the plasma levels of both beta-carotene and alpha-tocopherol and increasingly severe graded cervical histopathology. In groups with advanced dysplasias, the percentage of smokers was markedly increased and the women were comparatively older (p less than 0.0001). A strong association was noted between smoking status and plasma beta-carotene levels, independent of cervical pathology. However, this was not evident with respect to alpha-tocopherol. The findings suggest that the antioxidants beta-carotene and alpha-tocopherol have biologic functions that are interdependent in the pathogenesis of cervical intraepithelial lesions and cervical cancer.

Adolescent

Plasma ascorbic acid and beta-carotene levels in women evaluated for HPV infection, smoking, and cervix dysplasia.

The association of the plasma levels of the essential micronutrients, ascorbic acid and beta-carotene, with smoking and human papillomaviruses (HPV) infection has been studied in 75 women referred to a colposcopy clinic for an abnormal Pap smear. Each patient had a repeat Pap smear and a colposcopically directed biopsy of a visually perceived cervix abnormality. Cervicovaginal lavage specimen and peripheral venous blood sample were obtained for HPV DNA hybridization studies and nutrient analyses, respectively. Samples were obtained and analyzed without knowledge of each woman's clinical status. A group of 45 subjects had histopathologically diagnosed dysplasias of varying grades of severity. Among women with dysplasias, 53.3% were smokers. Of subjects with and of subjects without dysplasias, 66 and 34%, respectively, were positive for HPV infection. The mean plasma reduced ascorbic acid, retinol, and beta-carotene levels between the dysplastic groups were comparable. A strong association with smoking history and plasma reduced ascorbic acid level was note independent of cervical dysplasias or HPV status. The findings underscore the importance of smoking, ascorbic acid, and beta-carotene as nutritional variables, and HPV infection in the pathogenesis of cervical dysplasias.

Adult

Smoking and the antioxidant ascorbic acid: plasma, leukocyte, and cervicovaginal cell concentrations in normal healthy women.

The influence of cigarette smoking on the plasma, leukocyte, and cervicovaginal cell ascorbic acid levels in 46 healthy smokers and healthy nonsmokers was investigated. Coded peripheral venous blood and cervicovaginal lavage specimens obtained after informed consent were analyzed simultaneously for their ascorbic acid content. The findings suggest that smoking affects the levels and distribution of ascorbic acid. In smokers (n = 16), the number of exfoliated cervicovaginal epithelial cells and leukocyte ascorbic acid levels was significantly higher (p less than 0.01, p less than 0.05, respectively) compared with nonsmokers (n = 30). In addition, cervicovaginal cell ascorbic acid, plasma reduced and total ascorbic acid levels were significantly lower (p less than 0.001, p less than 0.01, p less than 0.01, respectively). The exfoliated epithelial cell ascorbic acid levels in nonsmokers was fourfold greater than that of leukocytes. The implications of these findings within the context of free radical-induced cellular pertubations in smokers are discussed.

Adult

Measurements of ascorbic acid and glutathione in exfoliated cervicovaginal epithelial cells of smokers and women with cervical dysplasias.

This report emphasizes the ability to quantify ascorbic acid (AA) and reduced glutathione (GSH) levels in exfoliated cervicovaginal epithelial cells obtained by a lavage technique. Sixty-two women with abnormal Papanicolaou smears underwent colposcopic examinations. Colposcopic lesions were biopsied and histopathologically graded. Marked variations in the number of cells and in the levels of AA and GSH were observed. In cigarette smokers, the number of exfoliated cells retrieved was significantly higher (p less than 0.05, by Student's t test). The simultaneous investigation of biochemical and virologic parameters in exfoliated cervicovaginal epithelial cells, in conjunction with the known cytopathologic and epidemiologic risk variables, provides a novel approach to elucidate factor(s) that may inhibit or promote cervical carcinogenesis in designed prospective studies.

Adult

Effects of smoking and oral contraception on plasma beta-carotene levels in healthy women.

Oral contraceptive use and smoking have been known to affect plasma vitamin levels. Total carotenoids have been studied with spectrophotometry, a relatively insensitive technique. In this study plasma concentrations of beta-carotene and retinol were measured in coded samples by sensitive high-pressure liquid chromatography in a cross-sectional study of 149 normal healthy women attending a family planning clinic. At the time of recruitment in the morning, a general health questionnaire was administered for patient age, methods of contraception, smoking habits, and food intake at breakfast. Of the 149 enrolled volunteers, 88 were oral contraceptive users and 61 were not users. Among users, 21 smoked cigarettes, and there were 18 smokers among nonusers. Oral contraceptive users had significantly lower plasma concentrations of beta-carotene (p less than 0.001) and higher retinol levels (p less than 0.0001). Plasma beta-carotene or retinol levels did not differ among users of intrauterine contraceptive devices or barrier methods of contraception. No association was noted between the plasma levels of these two micronutrients and age greater than or less than 30 years. Cigarette smoking alone was associated with significantly reduced plasma beta-carotene levels in nonusers (p less than 0.001). Combined cigarette smoking and oral contraceptive usage were associated with low plasma beta-carotene levels; the results appear to be additive. These findings suggest a possible synergistic effect on plasma beta-carotene levels from the use of both cigarette smoking and oral contraception.

Adolescent

Decreased beta-carotene tissue levels in uterine leiomyomas and cancers of reproductive and nonreproductive organs.

The dietary importance of beta-carotene as a factor in health maintenance has recently attracted considerable interest. Previously, total carotene content was estimated in a limited number of human tissues by means of spectrophotometric methods. In this study the levels of beta-carotene were measured by high-pressure liquid chromatography in tissue samples of uterine leiomyomas and adjacent normal myometrium obtained at hysterectomy from uteri of 18 patients. beta-Carotene concentration was significantly (p = 0.0013) lower in fibroid tissue than in normal myometrium. In addition, levels of beta-carotene were assayed in tissue samples of cancers of the cervix, endometrium, ovary, breast, colon, lung, liver, and rectum and were compared with levels of respective adjacent normal sites. The concentrations of beta-carotene were found to be lower in all cancer tissues. The decreased levels of beta-carotene suggest that beta-carotene deficiency may have a role in the cause and/or pathogenesis of leiomyomas and cancers of the organs that were investigated. The mechanism of action, however, remains unknown.

Adult

Plasma reduced and total ascorbic acid in healthy women: effects of smoking and oral contraception.

This is the first report of both reduced (RAA) and total (TAA) plasma ascorbic acid levels in women who smoke and are on oral contraception. 155 normal healthy subjects were investigated. A study questionnaire was completed including age, method of contraception, smoking status, and food intake at breakfast, prior to attending the clinic. Biochemical assays were promptly carried out without knowledge of subject's clinical or dietary status. One-way analysis of variance revealed that oral contraception per se, barrier or IUD methods have no effect on plasma ascorbic acid levels. The mean values (mg/dl +/- SD) for plasma RAA between smokers and nonsmokers were 0.512 +/- 0.241 and 0.601 +/- 0.263; and that for TAA were 0.565 +/- 0.232 and 0.682 +/- 0.231, respectively. Significant decreases in both plasma RAA (p less than 0.05) and TAA levels (p less than 0.001) were observed in smokers. Age was an interacting variable. No association of smoking or oral contraceptive use was seen with RAA or TAA levels among women less than 26 years, but decreases in both RAA and TAA levels were evident among smokers aged 26 years or older. The present study emphasizes the total exposure to smoking, e.g., pack years, is a significant confounding variable in the study of plasma ascorbic acid levels.

Adolescent

Colposcopic and cytologic detection of chronic lymphocytic leukemia.

We report the finding of chronic lymphocytic leukemia (CLL) in the cervix and vulva diagnosed during a gynecologic work-up of postmenopausal bleeding. Cervical cytology showed atypical lymphocytes. Colposcopic examination of the cervix identified an abnormal area. A colposcopically directed punch biopsy revealed a lymphoproliferative infiltrate consistent with CLL.

Aged

Plasma retinol-binding protein in human uterine cervical dysplasias and cancer.

Plasma concentrations of retinol-binding protein (RBP) were measured in a cross-sectional study of asymptomatic normal menstruating women (n = 94) who obtained Pap smears and participated in a double-blinded nutritional survey. Controls (n = 45) were women with negative cervical cytology, normal colposcopy and no known gynecologic pathology or dysfunction. Cases (n = 49) were subjects with abnormal cytology and colposcopically directed biopsy that established cervical epithelial dysplasias histopathologically in the previous 12-month period. In addition, 8 women with cancer of the cervix were also investigated. The mean plasma concentration of RBP was significantly lower in cases than in controls (p less than 0.001). In normal females, the follicular phase of the menstrual cycle was increased. This increase was absent in the plasma of patients with cervical dysplasias (p less than 0.05). The data direct attention to a possible etiologic association between RBP in human cervical epithelial abnormalities and cancer.

Adult

Detection of human papillomavirus deoxyribonucleic acid in exfoliated cervicovaginal cells as a predictor of cervical neoplasia in a high-risk population.

Specific types of human papillomavirus are currently implicated as etiologic agents of precancerous and cancerous lesions of the cervix. We have previously described the use of cervicovaginal lavage and molecular hybridization to detect human papillomavirus infections of the cervix. We report here the predictive value of this method of human papillomavirus detection to identify women with biopsy proved dysplastic and cancerous lesions of the cervix. One hundred ninety-one women from a city hospital colposcopy clinic underwent concurrent Papanicolaou smear, cervicovaginal lavage, and coloposcopically directed cervical biopsy. Human papillomavirus deoxyribonucleic acid was detected in 114 (59.7%) of these women. Of the positive results, human papillomavirus type 16 accounted for 23.7%, human papillomavirus type 18 for 10.5%, human papillomavirus type six or 11 for 6.2%, related human papillomavirus types for 52.6%, and 7.0% contained more than one type. The distribution of human papillomavirus types was similar in both women younger than 40 years of age and in older women. Eighty-nine of 128 (69.5%) women less than 40 years old with cervical lesions had positive findings of human papillomavirus, and 18 of 29 (62.1%) older women with cervical lesions had positive findings of human papillomavirus. Detection of human papillomavirus types 16 and 18 identified only 35 of 157 (22.3%) women with cervical lesions. The sensitivity of detecting all types of human papillomavirus as a predictor of a biopsy proved lesion (68.0%) was comparable with the sensitivity of cytologic examination alone (74.0%). However, human papillomavirus detection combined with the Papanicolaou smear provided an increased overall sensitivity of 89.3% (p less than 0.01). In fact, women either positive for human papillomavirus or having abnormal cytologic findings were 11.8 times more likely to have a biopsy proved cervical lesion than human papillomavirus-negative women with negative cytologic results (95% confidence interval for odds ratio: 5.3 to 26.6). We conclude that the sensitivity of cytologic examination plus human papillomavirus detection is superior to the use of either cytologic studies or human papillomavirus detection alone in identifying patients with cervical lesions.

Adolescent

Vaginal hydrolysis of retinyl acetate: increase in plasma retinol and retinol binding protein in women with cervical dysplasias.

We previously reported the clinical feasibility of a Phase I trial involving the topical administration of a RA gel applied cervicovaginally in women with mild or moderate cervical dysplasia. Now, we report hydrolysis and systemic absorption of the RA gel from the vagina. HPLC analysis of samples of residual gel obtained from the cervical canal after topical bolus application indicate that the RA undergoes prompt in vivo hydrolysis yielding retinol as a major metabolite. Venous blood samples of 41 subjects, who self-administered a RA gel, were analyzed for plasma retinol and RBP concentrations prior to and upon completion of a 7-day treatment course and upon return for follow-up examinations. An increase in both the concentrations of plasma retinol and RBP were detected after topical application of the RA gel. These elevated values receded after the gel administration was discontinued. No significant changes were observed in plasma retinol or RBP concentrations in placebo-treated subjects. The efficacy of RA as a chemopreventive agent in treating cervical dysplasias remains to be determined.

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